2-substituted pi system derivatives of adenosine that are coronary vasodilators acting via the A2A adenosine receptor

Nucleosides Nucleotides Nucleic Acids. Apr-Jul 2001;20(4-7):343-60. doi: 10.1081/NCN-100002306.

Abstract

Compound 20 (CVT-3146--a 2-[(N-1-(4-N-methylcarboxamidopyrazolyl)] adenosine derivative) and compound 31 (CVT-3033--a 2-[(4-(1-N-pentylpyrazolyl)] adenosine derivative), were found to be short acting functionally selective coronary vasodilators (CV t0.5 = 5.2 +/- 0.2 and 3.4 +/- 0.5 min, respectively--rat isolated heart 50% reversal time) with good potency (EC50S = 6.4 +/- 1.2 nM and 67.9 +/- 16.7 nM, respectively), but they possess low affinity for the ADO A2A receptor (Ki = 1122 +/- 323 nM and 2138 +/- 952 nM, respectively; pig striatum).

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Animals
  • Brain / metabolism
  • Coronary Vessels / drug effects*
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Models, Molecular
  • Purinergic P1 Receptor Agonists*
  • Rats
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1 / metabolism
  • Structure-Activity Relationship
  • Swine
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / metabolism
  • Vasodilator Agents / pharmacology*

Substances

  • Purinergic P1 Receptor Agonists
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1
  • Vasodilator Agents
  • Adenosine